The crosstalk between aldosterone and calcium metabolism in primary aldosteronism: A possible calcium metabolism-associated aberrant “neoplastic” steroidogenesis in adrenals

Gao, Xin; Yamazaki, Yuto; Tezuka, Yuta; Onodera, Yoshiaki; Ogata, Hiroko; Omata, Kei; Morimoto, Ryo; Nakamura, Yasuhiro; Satoh, Fumitoshi; Sasano, Hironobu

doi:10.1016/j.jsbmb.2019.105434

Cited by 27 publications

(31 citation statements)

References 34 publications

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“…CYP11B2 is considered as a marker of aldosterone synthesis and widely believed with upregulated expression in APA. Besides, the other three DEGs, PCP4, HTR4 and VDR also have been reported to be involved in the occurrence and development of APA [11][12][13] , and among them, the upregulated expression of HTR4 was veri ed by the qPCR in this study. HTR4 is a serotonin receptor subtype known to be expressed in adrenal gland, and serotonin acted on the receptor can increase aldosterone secretion in vivo and in vitro [14][15][16] .…”

Section: Discussionsupporting

confidence: 53%

The Bioinformatics Analysis of Aldosterone-Producing Adenoma and Verification of Differentially Expressed Genes

Gao

Wang

et al. 2021

Preprint

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BackgroundPrevious studies have investigated the transcriptional modulations of aldosterone overproduction of aldosterone-producing adenomas (APAs), and several potential genes were found with high expressions. PurposeWe aimed to systematically study the genes and pathways associated with molecular mechanism underlying APA by bioinformatics analysis and experimental validation for the expression profile. MethodsThis study was performed based on three gene expression profiles (GSE64957, GSE8514, and GSE60042). Differentially expressed gene (DEG) investigation, function and pathway enrichment, as well as protein-protein interaction (PPI) network, were performed by the bioinformatics analysis. For the validation with quantitative PCR, tissues from 11 patients with non-functioning adrenal adenoma (NFA) and 13 with APA were included in our cohort. ResultsIn this study, the bioinformatics analysis was performed and 182 upregulated and 88 downregulated DEGs were identified. As expected, the upregulated DEGs were primarily involved in calcium ion homeostasis (GO: 0055074, n = 3, p = 2.00X10-4). In the KEGG pathway analysis, calcium signaling pathway (hsa04020, n = 8, p= 4.38X10-6) and the aldosterone synthesis and secretion (hsa04925, n = 6, p = 8.73X10-6) were enriched. Moreover, quantitative PCR was performed to detect the expression of 7 upregulated genes (PCP4, ATP2A3, CYP11B2, CLCN5, HTR4, VDR and AQP2) among the intersection of DEGs. The mRNA levels of CYP11B2, HTR4 and AQP2 were significantly increased in APA samples compared to NFA (24.420 folds of NFA, p<0.001, 3.753 folds of NFA, p=0.002 and 11.487 folds of NFA, p=0.018).ConclusionIn summary, the present study showed several candidate genes with high expression from bioinformatics analysis and our cohort. And the DEGs were enriched in aldosterone synthesis and secretion and calcium signaling pathway as expected.

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Section: Discussionsupporting

confidence: 53%

The Bioinformatics Analysis of Aldosterone-Producing Adenoma and Verification of Differentially Expressed Genes

Gao

Wang

et al. 2021

Preprint

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“…Third, a genome-wide study focused on identifying new candidate genes associated with osteoporosis indicated that genes involved in aldosterone signaling in epithelial cells may be linked to osteoporosis, supporting the potential relationship between aldosterone and bone (36). Moreover, a very recent study immunolocalized Ca metabolism-related receptors (calcium sensitive receptor, vitamin D receptor, and PTH receptor) in normal adrenal glands and aldosterone-producing adenomas, which demonstrated that aldosterone biosynthesis was regulated by calcium (37). Therefore, excess aldosterone biosynthesis may be related to bone resorption.…”

Section: How Does Excessive Aldosterone Affect Bone Metabolism?mentioning

confidence: 91%

Primary Aldosteronism and Bone Metabolism: A Systematic Review and Meta-Analysis

Shi

Tian

et al. 2020

Front. Endocrinol.

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Background: Currently, increasing evidence shows that excess aldosterone may have an impact on bone health, and primary aldosteronism (PA) may be a secondary cause of osteoporosis. This problem is worthy of attention because secondary osteoporosis is always potentially reversible, which affects the selection of treatment for PA to some extent. The present systematic review will assess and summarize the available data regarding the relationship between PA and osteoporosis. Methods: Pubmed and Embase were searched for clinical trials related to the association between PA and bone metabolism. The results were limited to full-text articles published in English, without restrictions for the publication time. The quality of clinical trials was appraised, and the data were extracted. Biochemical parameters of bone turnover in PA patients were assessed using random-effect meta-analysis. Descriptive analysis was performed for other parameters, for data is insufficient. Results: A final total of 15 articles were included in this review. The meta-analysis of six studies showed that subjects with PA had higher serum PTH levels (MD=21.50 pg/ml, 95% CI (15.63, 27.37), P<0.00001) and slightly increased urinary calcium levels (MD = 1.65 mmol/24 h, 95% CI (1.24, 2.06), P < 0.00001) than the EH controls. PA is associated with an increased risk of bone fracture. Bone loss in patients with PA may be reversed by MR antagonists or adrenal surgery. Conclusions: PA may be a secondary cause of osteoporosis and is associated with an increased risk of bone fracture. The clarification of the relationships between PA and bone metabolism requires additional prospective randomized controlled studies in a large sample.

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“…Microvascular density (MVD) was evaluated by counting the number of CD31-positive vessels within 0.75 mm 2 and highest expressed tumor area ( 24 ). Immunoreactivity of catecholamine-synthesizing enzymes including tyrosine hydroxylase (TH), dopa-decarboxylase (DDC), and phentolamine-N-methyltransferase (PNMT) was all digitally and quantitatively evaluated by using “HALO™ CytoNuclear ver.1.5” (Indica Laboratories, Corrales, NM, USA) image analysis ( 25 , 26 ). The positive cells were tentatively classified into the following four categories based on the levels of their relative immunointensity: negative as “0”, weak as “+1”, moderate as “+2”, and strong as “+3”.…”

Section: Methodsmentioning

confidence: 99%

Histopathological Analysis of Tumor Microenvironment and Angiogenesis in Pheochromocytoma

et al. 2020

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The crosstalk between aldosterone and calcium metabolism in primary aldosteronism: A possible calcium metabolism-associated aberrant “neoplastic” steroidogenesis in adrenals

Cited by 27 publications

References 34 publications

The Bioinformatics Analysis of Aldosterone-Producing Adenoma and Verification of Differentially Expressed Genes

The Bioinformatics Analysis of Aldosterone-Producing Adenoma and Verification of Differentially Expressed Genes

Primary Aldosteronism and Bone Metabolism: A Systematic Review and Meta-Analysis

Histopathological Analysis of Tumor Microenvironment and Angiogenesis in Pheochromocytoma

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